BMD-Related Genetic Risk Scores Predict Site-Specific Fractures as Well as Trabecular and Cortical Bone Microstructure.
Aged
Bone Density
/ genetics
Cancellous Bone
/ metabolism
Case-Control Studies
Cohort Studies
Cortical Bone
/ metabolism
Female
Follow-Up Studies
Fractures, Bone
/ diagnosis
Humans
Male
Middle Aged
Osteoporosis
/ diagnosis
Polymorphism, Single Nucleotide
Prognosis
Risk Factors
Spinal Fractures
/ diagnosis
bone microstructure
bone mineral density
cortical
fractures
genetic risk scores
trabecular
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 04 2020
01 04 2020
Historique:
received:
13
11
2019
accepted:
14
02
2020
pubmed:
19
2
2020
medline:
5
1
2021
entrez:
19
2
2020
Statut:
ppublish
Résumé
It is important to identify patients at highest risk of fractures. To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately. Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs). Associations between these GRSs and forearm (ncases = 1020; ncontrols = 2838), hip (ncases = 1123; ncontrols = 2630) and vertebral (ncases = 288; ncontrols = 1187) fractures were evaluated in 3 Swedish cohorts. Associations between the GRSs and trabecular and cortical bone microstructure parameters (n = 426) were evaluated in the MrOS Sweden cohort. We found that eBMDGRS was the only significant independent predictor of forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS were significant independent predictors of hip fractures. The eBMDGRS was the major GRS contributing to prediction of trabecular bone microstructure parameters while both FN-BMDGRS and eBMDGRS contributed information for prediction of cortical bone microstructure parameters. The eBMDGRS independently predicts forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS contribute independent information for prediction of hip fractures. We propose that eBMDGRS captures unique information about trabecular bone microstructure useful for prediction of forearm and vertebral fractures. These findings may facilitate personalized medicine to predict site-specific fractures as well as cortical and trabecular bone microstructure separately.
Identifiants
pubmed: 32067027
pii: 5739622
doi: 10.1210/clinem/dgaa082
pmc: PMC7069346
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© Endocrine Society 2020.
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